Parkinson‐like early autonomic dysfunction induced by vagal application of DOPAL in rats

• Published in: CNS neuroscience & therapeutics Vol. 27; no. 5; pp. 540 - 551
• Main Authors: Sun, Jie, He, Chao, Yan, Qiu‐Xin, Wang, Hong‐Dan, Li, Ke‐Xin, Sun, Xun, Feng, Yan, Zha, Rong‐Rong, Cui, Chang‐Peng, Xiong, Xue, Gao, Shan, Wang, Xue, Yin, Rui‐Xue, Qiao, Guo‐Fen, Li, Bai‐Yan
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.05.2021; John Wiley and Sons Inc
• Subjects: 3,4-Dihydroxyphenylacetic Acid - analogs & derivatives; 3,4-Dihydroxyphenylacetic Acid - pharmacology; alpha-Synuclein - biosynthesis; alpha-Synuclein - genetics; Animals; autonomic dysfunction; Autonomic Nervous System Diseases - etiology; Autonomic Nervous System Diseases - pathology; Baroreceptors; Baroreflex - drug effects; Blood pressure; Blood Pressure - drug effects; Cardiomyocytes; DOPAL; Dopamine; Dysautonomia; Echocardiography; Electrocardiography; Etiology; Gene expression; Hypotension; Hypotension, Orthostatic - physiopathology; Laboratory animals; Male; Mitochondria; Mitochondria, Heart - pathology; Movement disorders; Myocardium - pathology; Myocytes, Cardiac - pathology; Neurodegenerative diseases; Nodose Ganglion - pathology; Original; Parkinson Disease, Secondary - complications; Parkinson Disease, Secondary - pathology; Parkinson's disease; Rats; Rats, Sprague-Dawley; Reflexes; Solitary tract nucleus; Synuclein; Ultrastructure; vagus; Vagus Nerve; α‐synuclein; DOPAL; Parkinson's disease; autonomic dysfunction; vagus; α-synuclein
• ISSN: 1755-5930; 1755-5949; 1755-5949
• DOI: 10.1111/cns.13589

Aim To understand why autonomic failures, a common non‐motor symptom of Parkinson's disease (PD), occur earlier than typical motor disorders. Methods Vagal application of DOPAL (3,4‐dihydroxyphenylacetaldehyde) to simulate PD‐like autonomic dysfunction and understand the connection between PD and cardiovascular dysfunction. Molecular and morphological approaches were employed to test the time‐dependent alternation of α‐synuclein aggregation and the ultrastructure changes in the heart and nodose (NG)/nucleus tractus solitarius (NTS). Results Blood pressure (BP) and baroreflex sensitivity of DOPAL‐treated rats were significantly reduced accompanied with a time‐dependent change in orthostatic BP, consistent with altered echocardiography and cardiomyocyte mitochondrial ultrastructure. Notably, time‐dependent and collaborated changes in Mon‐/Tri‐α‐synuclein were paralleled with morphological alternation in the NG and NTS. Conclusion These all demonstrate that early autonomic dysfunction mediated by vagal application of DOPAL highly suggests the plausible etiology of PD initiated from peripheral, rather than central site. It will provide a scientific basis for the prevention and early diagnosis of PD. Application of DOPAL on Vagus causes significant accumulation of α‐Syn monomers to form toxic oligomers that could be transported to the heart TA and NG‐NTS by axon flow